DESCRIPTION: The goal of this project is to understand the mechanism of chromosome segregation in yeast. Defining this process will be essential for understanding the basis for the defects in chromosome segregation observed in cancer cells. Our approach is to use the facile genetics of yeast to identify genes required for anaphase, determine the molecular function of the cloned genes, and define the cell cycle control of the encoded proteins. This laboratory has identified Ase1, a novel spindle component that localizes to the midzone of the anaphase spindle. The analysis of ase1 mutants suggests that Ase1 plays a key role in maintaining the interaction between the two halves of the anaphase spindle. Recently, we have found that the expression of Ase1 is strikingly similar to that of yeast B-type cyclins. ASE1 is both coordinately transcribed with B-type cyclins and is also abruptly degraded at the end of mitosis. In both yeast cells and Xenopus egg extracts we have found that the cell cycle-specific degradation of Ase1 is mediated by the Anaphase Promoting Complex (APC), the regulatory apparatus that targets cyclins for ubiquitination and subsequent degradation. Our observations on Ase1 regulation suggest a mechanism for how different stages of mitosis might be ordered: stage-specific events may be dependent upon the regulated expression of rate-limiting components. To characterize what may be the first of a number of cyclin-like spindle proteins in yeast, we propose experiments to determine the molecular function of Ase1, to characterize its cell cycle-specific regulation, and to characterize genes that are required with ASE1 for chromosome segregation.